Introduction: Chinese Yam (Dioscoreae Rhizoma), one of well-known traditional edible and medical homologous foods, have been used to treat various diseases for a long time. Network pharmacology is a valuable tool for studying multi-indications in Chinese medicines. However, a holistic network pharmacology approach to understanding the efficacy and mechanism of Chinese Yam has not been pursued. In this study, we explored the underlying pharmacological properties and possible application of Chinese Yam for the treatment of senility and cancer. Methods: The compounds and targets of Chinese Yam were predicted by using BATMAN-TCM, PubChem and Swiss Target Prediction database. The molecular docking experiments were performed by using AutoDock Vina (v1.1.2) after the top 5 targets of PPI were screened through String database. g:Profiler website was adopted to conduct GO functional and KEGG pathway enrichment analysis, while the advanced bubble diagrams and mechanisms maps were respectively drawn by OmicShare Tools and Edraw software. The PPI network and D-C-T-P network were constructed by utilized Cytoscape 3.7.0 software. Results: Total 20 compounds were collected in BATMAN-TCM and transformed into 19 unique Canonical SMILES. After removing the duplicates, 134 predicted targets were obtained via Swiss Target Prediction. And 104 key targets were screened out through PPI network and Cytoscape software, among which the top 5 targets were used for molecular docking. It was shown that MAPK3-campesterol, RXRA-cholesteryl ferulate, RXRA-stigmasterol and STAT3-cholesteryl ferulate could be well bonded. Moreover, according to the gene numbers, the top 30 bubble chart of GO enrichment terms were made. The enriched cell components included organelle, membrane−bounded organelle, cytoplasm, etc. Biological processes enriched of Chinese Yam mainly covered biological regulation, responses to stimulus, metabolic process, etc. The enrichment of molecular function involved in protein binding, ion binding, organic cyclic compound binding, etc. And 35 enrichment pathways were screened out, including Notch signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, etc. The 84 same targets in the compounds and enrichment pathways of Chinese Yam were collected, and D-C-T-P network was constructed and showed the visualization of potential mechanisms. Conclusion: Chinese Yam was used to treat aging-related diseases through a complex network. Its key active compounds could inhibit tumor proliferation and metastasis, regulate metabolism and promote nerve repair through regulating the expression of targets(MAPK3, HADC3, HADC1, RXRA, STAT3, etc.) via multiple pathways, Notch signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, etc. © 2020 Elsevier GmbH